Medivir AB (publ) (MVIR) Earnings Call Transcript & Summary

Welcome to Medivir Q1 report. [Operator Instructions] Now I will hand the conference over to the speakers. CEO, Jens Lindberg, please go ahead.

Thank you, and welcome, everyone, to the Medivir quarter 1 webcast. Let's move forward. I will be taking most of the presentation, but in the room with me, when as we move into the question-and-answer session is our CFO, Magnus Christensen, and I'm also joined by our recently joined CMO, Pia Baumann; and our CSO, Fredrik Öberg. So with that, let's move into the events of quarter 1. Important information, as always, you'll find the presentation on our website, and you can have a look at the information there. Quarter 1 has been a very good quarter from a Medivir's perspective, both with regards to our main in-house project, fostrox and our pipeline projects. And if we look at the fostrox development as a first go, we've seen that development pick up speed quite nicely in the first quarter. We were able to establish the recommended Phase 2 dose for the first combination arm, which was for fostrox and Lenvima, where we were able to dose up to 30 milligram. In addition, we were able to sort of very quickly turn that around as we moved into Phase 2a, the expansion phase and had the first patient dosed very quickly upon initiation. Encouraging and we'll go into some of the -- a little bit more details today than we've had in previous calls. Our longest running patient still on treatment, is now sort of longer than 8 months without disease progression. And again, as I said, a bit more details in a little bit. We're seeing very rapid recruitment in the expansion phase for the fostrox plus Lenvima arm. We now have 5 patients already dosed, and we have an additional 6 patients in screening after -- or 6 weeks after initiation. So moving along very nicely, strong interest from clinicians and patients. In addition, we recently presented new data showing synergistic efficacy of fostrox in a triple combination with PD-1 and TKI, or kinase inhibitor in tumor models, which our CSO, Fredrik Öberg presented at the AACR conference. And we'll come back to that data and the importance of that data in a little bit as well. If we leave fostrox for a couple of minutes and when we look at the other portfolio, encouraging process across those projects as well. We -- IGM Biosciences who has licensed the birinapant molecule. They recently announced that they have completed the fourth dose escalation cohort in the combination study of birinapant with their DR5 agonist IGM-8444. Encouraging, no DLTs observed to date. And they have also started dosed up sort of further in the birinapant -- with the birinapant molecule. So they are now enrolling in cohort number 5. We -- I mentioned that we presented data at AACR, similarly, our partner Tango Therapeutics who previously licensed our preclinical USP1 program. They presented data at the AACR conference as well, showing both single-agent activity as well as sort of synergy with PARP inhibitor for the molecule, now named TNG348. And they reiterated their intention to file for an IND in mid-2023. So they're moving into the clinic in 2023. And finally, our partner, INFEX Therapeutics, they received the FDA QIDP designation for the MET-X program in early January. So nice movement across the entire portfolio in quarter 1. If we tied into -- this is -- sorry, the pipeline overview. And as we always do, our focus is on fostrox. Hence, we will spend most of our time today going through that program and digging into a bit more detail, and we will touch a little bit on the pipeline overview as well -- or the other projects as well. But if we move into our main project, fostrox, as we have outlined before, this is the program as we are running it currently. And on the left-hand side of the slide, there is the Phase I data, where we showed sort of benefit as a monotherapy, but then we quickly moved into combination as we believe that fostrox will bring the greatest clinical benefit in combination with other compounds or other mechanisms of action. And this is where we now are. We've -- as mentioned, we communicated in Q1 that we -- sort of identified the recommended Phase 2 dose for the first combination arm of fostrox plus Lenvima. The other combination of fostrox plus pembrolizumab is still in Phase 1b. So we haven't sort of set the recommended Phase 2 dose yet. So that arm is still ongoing. But as I mentioned, encouragingly, we dosed up to 30 milligrams in the fostrox combination with Lenvatinib without DLTs. And we have now sort of rapidly moved into the Phase 2a expansion phase. And if we go into that part, let's focus a bit more on the Lenvatinib arm considering that has sort of come the furthest along in development. On the left-hand side -- and let's look at a bit more detail on the left-hand side. As I mentioned, we've had a rapid inclusion in the first 6 weeks of that sort of Phase 2a study. So with those 5 patients already, we have 6 patients in screening. And as a reference, we have 4 patients in screening on Monday. So 2 more patients have entered screening during the week. So again, strong interest in this arm from clinicians and from patients. And I will touch a little bit on that, why we are seeing that interest because there's a natural -- so there are a couple of sort of natural reasons why that arm is moving along with such speed. But we wanted to take a little bit of -- take an opportunity to give a bit more details on what we are seeing sort of from the fostrox lenvatinib sort of dose cohort to dose cohorts. And 2 patients, just to sort of give a little bit of a sample. Patient number 1 is a female Caucasian patient relatively sort of young, 56 years of age, and has a viral driven sort of hepatitis C-driven liver cancer. She came -- she entered fostrox plus lenvatinib in the first dose cohort of 20 milligram and she had previously progressed on first-line treatment of Tecentriq plus Avastin, and she progressed after 6 -- sorry, 5 months. She's still on treatment after sort of a little over 8 months without disease progression. So encouraging ability to both stay on drug and also to stay on drug with and without sort of disease progression in a quite long time, and we'll make a bit of a comparison on that sort of on the next slide. And clearly, sort of 1 patient only on this one, but encouragingly that they've been able to sort of stay without progression sort of longer than the first line treatment. The second patient is a little bit of the opposite from a demographics perspective, male patient, Asian, descent, older, 71 years of age and also sort of despite being Asian, non-viral-driven HCC, where most of the patients from the Asian population are viral driven, but this is a non-viral driven. He progressed on first-line to Tecentriq plus Avastin as well, and that's pretty much what we see. Most of the patients going into the fostrox lenvatinib arm, they come in after having progressed on Tecentriq plus Avastin. He progressed quickly after 1.5 months. Starting on lenvatinib, sort of for the first week because that's what they do. They start sort of 1 week ahead of fostrox. The patient incurred side effects on lenvatinib after sort of 2 or 3 days and they sort of stopped the lenvatinib treatment. But the center decided to keep the patient on -- or keep the patients to initiate fostrox anyway. So this patient has not counted towards the dose cohorts but has stayed on fostrox monotherapy. So it's a bit of an outlier, but it's interesting to follow to see because this patient is only getting fostrox from the treatment perspective. And again, he is -- sort of now 6 months into treatment without disease progression. He came in on the fostrox cohort of 30 milligram. So again, sort of encouraging to see individual patients are staying on treatment for such a long period of time. Clearly, sort of it goes without saying that not all patients will have the same sort of benefit. Have we seen patients sort of progressing earlier? Yes, of course, we have. But I think it's an interesting perspective because if we dive into what has been shown in this sort of second line advanced HCC patient population before. And across the studies regardless of whether you look at PD-1s or kinase inhibitors, the response rates and then more importantly, the progression-free survival time is quite short. So it's a very difficult population with regards to treatment. And there's also a good chunk of patients that are not able to move into second line. So when they move into second line, they are able to sustain treatment and benefit for 6 months and longer. Clearly, that's highly encouraging. So this is sort of the fact that the response rates and the PFS time lines are quite short, signals a very high unmet medical need. So if we then start to look ahead because now we're recruiting into Phase 2a with speed and our aim is sort of clearly to progress beyond Phase 2a. And as we've communicated before, we are looking to select the best combination arm as we move into Phase 2b. So -- and trying to visualize this a bit. So we will be clearly looking at the data coming out of Phase 1b, Phase 2a, selecting the best combination arm. And -- when we say "best", which I've put in quotation marks here, that's because there are a few different factors influencing that selection. So on the one hand, safety and tolerability, of course, but also then clinical benefit for each combination arm. So those may go with -- goes without saying. But I think that an important element as well is that strategic fit in the treatment algorithm today, but more importantly, perhaps tomorrow, what will the second-line treatment population, treatment algorithm look like as we gaze into the future. And this is sort of schematically trying to show than -- that sort of treatment algorithm, where sort of HCC patients as they are diagnosed they are -- they will be diagnosed at different stages of the disease. And here, we talk about the advanced stage of Stage C, which I've highlighted with sort of the colors here. And we are currently evaluating that sort of second-line patient population. And what we are seeing, as I mentioned before, is that the majority of the patients in first line, they will receive the combination of Tecentriq plus Avastin. Guidelines recommended we see in our study that that's what they are getting. I actually believe that all of the patients on that so far on the fostrox lenvatinib arm also coming from Tecentriq plus Avastin. But importantly, what we are seeing as well is that the what are clinicians then doing today in that second-line patient population. And today, in clinical standard Lenvima is the preferred option. So that makes a combination with fostrox plus Lenvima, probably the most relevant one strategically as we look to sort of further develop fostrox in that second line population. And the fact that fostrox plus Lenvima arm is recruiting with such speed is quite encouraging as there are a number of factors or multiple factors favoring them the fostrox Lenvima arm as the best arm for second line. I alluded to it previously, but the ability to sort of dose up fostrox the 30-milligram in combination with Lenvima. And Lenvima can post its challenges from a side effect perspective, so that we are able to dose up to 30 is a very encouraging sign without DLTs. As I highlighted before, with a couple of sort of patient examples, it is encouraging with patients staying on treatment for such a long time in this very difficult-to-treat population. And then as I mentioned, the combination of fostrox plus Lenvima being aligned with treatment guidelines moving forward. And we feel that the steer from clinicians and KOLs are quite strong on this, that they see Tecentriq plus Avastin as the first-line option, Lenvima as a second-line option today, but also in sort of -- that sort of short to medium term, i.e., that's what we could be aiming for to fit in, hence fostrox plus Lenvima makes the most sense from a Phase 2b perspective. Hence and encouraging that arm is recruiting the fastest. It's -- the other arm -- the other combination arm identify -- the other arm of fostrox plus pembro, as I said, is still ongoing from a Phase 1b perspective. It's still recruiting. There is still interest in that arm. But I think it's fair to say that considering it's -- Lenvima see more as the preferred second-line option is one of the reasons why that specific arm is also recruiting faster, i.e., the fostrox plus Lenvima arm. One other element that is sort of new development that could be interesting in the longer term and also speaks in favor of Lenvima plus fostrox is recent data at AACR, where [ Roche ] presented results for Tecentriq plus Avastin as adjuvant therapy, i.e., after surgery. So on the left-hand side, and I know that the slide is relatively small, but a positive results with regards to the relapse-free survival for Tecentriq plus Avastin versus sort of watch and wait i.e., the patients are benefiting from being treated with that combination for up to 12 months after surgery. But the other part that is quite interesting is on the slide on the right or the picture on the right, and that is that they can see and they've been able to see that patients coming out of surgery, there is 1 chunk of patients who will progress relatively quick, i.e., they will progress within the first year, they will progress while on adjuvant treatment with Tecentriq plus Avastin. And if you are progressing on Tecentriq plus Avastin and you move into a more advanced stage, then Tecentriq plus Avastin will not be a logical sort of treatment to use in that setting. That will then, for some patients, and it remains to be seen how many, that will move up Lenvima to more of a logic first-line option, hence, a combination of fostrox plus Lenvima could also then potentially -- sort of have potential for earlier line use as they sort of shift starts to happen. But again, this is sort of recently presented data, so it will take some time before it is approved but it's something to keep an eye on. And as I mentioned, it could provide another rationale as to why fostrox plus Lenvima at this stage is the more attractive arm to move forward with. With that said, we will not sort of then -- sort of as we move forward and we select them sort of the best combination arm for second line, there is a second arm, which we are not selecting. Does that mean that, that arm is not relevant? And that is not the case. So instead, there could be additions sort of other opportunities for combination for arm. And basically, what we see is that we're seeing a very clear trend towards triple combinations, and this is where -- this arm could play in. Because any dose that we set with pembrolizumab could inform combo dose potentially with other PD-1s or PD-L1s. And as you -- as I mentioned before, in the treatment that have algorithm, a majority of patients are getting Tecentriq plus Avastin combo in first line, we know that. The other part that we know is that many other combos or combinations of PD-1 and TKIs have tried to beat Tecentriq plus Avastin or show better efficacy and they haven't succeeded. Many have tried. No one has succeeded. So the conclusion we draw from that and the feedback we get from KOLs is that you -- if you want to reach -- if you want to sort of achieve something different, you need to do something different. So you need a different mode of action or additional modes of action to improve that benefit in first line. And since we know that sort of combine in chemotherapy, sort of with the PD-1 or the other mechanism could make a lot of sense and that could open up an opportunity to move into a triple combination opportunity. And this was sort of evidenced by the data that we also recently -- Fredrik, our CSO, recently presented at AACR conference. So basically, we showed 2 things. On the left-hand side, we show that sort of fostrox has the ability to induced expression of PD-L1, LAG3 and CD8, i.e., we're able to increase the immune-mediated antitumor activity. We -- and which then sort of leads to a situation where fostrox is able to basically help the PD-1 or PD-L1 do a better job as it has a positive effect on the tumor microenvironment. And on the right-hand side, we can see that, that is also sort of playing through. On this one, we tested fostrox with anti-PD-1 and Lenvima combination, and we can see in the graph here that sort of when you add fostrox to that PD-1 Lenvima combination, you see a synergistic efficacy and a clearly sort of improved benefit in that patient population. So encouraging to see what fostrox brings to the table from a triple combination perspective and something that we will -- we are and we need to sort of consider as we move forward. So we believe, as we've said before, and we know that fostrox is unique. We know it's sort of first-in-class potential treatment for primary liver cancer. It is different from the other treatments on the market where most of them are in either the PD-1 bucket or kinase inhibitor bucket. So being unique in an area of significant unmet need means that we do believe that has significant commercial potential. Being unique that there's also selectively targets cancer in the liver. So it's the only liver-directed one and therefore, also bypassing resistance mechanisms. But perhaps most importantly, it has very strong potential for attractive combinations across lines of treatment, whether it be double combination or triple combination. And again, as mentioned previously, very encouraging to see what we are seeing with the fostrox Lenvima combination so far in that second-line treatment. And as we move forward, as Pia has come on board as our CMO, we have also taken a step to establish a more of a formal scientific council that will support shaping our future development as we move towards Phase 2b and onwards, and we look towards different alternative combinations. It's important that we do that not in isolation, but that we do that with the expertise that is available, and we are super happy that these 5 physicians. where 3 of them, Dr. Reig, Dr. Evans and Dr. Heo are involved in our current study, and they are joined by Dr. Finn from the U.S. and Dr. Vogel from Germany as our 5 person strong scientific council, and we will sort of start to engage with them formally now and onwards to shape our future development. With that, I'll stop with fostrox and have few words on the clinical portfolio and partnerships before we also sort of handle the financial elements, of course. And the only slide I have on the additional sort of the other projects is on the TNG348, which is now the molecule name or the candidate name for the USP -- the selected USP-1, a candidate drug from Tango Therapeutics. And on the right-hand side, this is a part of the new data, and there's much more than that on the poster in which you can find on the Tango Therapeutics website. But basically, they show that the TNG348 molecule synergizes nicely in vivo with PARP inhibitor which we knew. And we also -- they've also been able to show that it can overcome PARP inhibitor resistance. So that opens up a nice sort of commercial opportunity in a relatively sort of big population across multiple tumor types. So very encouraging data, and Tango then also reiterated that they are moving with as much speed as they can, and they plan to file for an IND mid-2023. So not far away now. And with that, we move into the financial highlights. Magnus?

Thank you, Jens. If we can move to Slide #23, where you can see the financial summary for quarter 1 this year, which I will briefly comment on. All numbers are in million SEK. From a financial viewpoint, Q1 was pretty straightforward quarter this year, in line with our current plan. The turnover was SEK 0.4 million and which relates entirely to royalty income that we received for Xerclear. And it's on principally the same level as last year. Other external expenses amount to minus SEK 13 million in Q1 and it's significantly lower compared to last year and it relates foremost to lower clinical costs. As last year, we had high clinic costs for the combination study, which was more or less in the start-up process. The personnel costs are in line with last year and according to our plan. The operating loss for Q1 is almost minus SEK 20 million and lower compared to last year. And as I mentioned, foremost due to the lower clinical costs that we have. The cash flow from the operating activities in Q1 amounts to minus SEK 16 million, which is in line with our current plan, and it's much lower than last quarter last year. And to sum up, the cash position in the end of Q1 is around SEK 101 million. And according to the current plan and with our current assumption, the cash run rate is into Q2 next year. And with this, I will hand back over to Jens again.

Thank you, and we will wrap things up by moving back to the highlights slide. And I think that sort of overall, as I hopefully been able to convey, we feel very happy about sort of the progress in the first quarter. Clearly, our main focus is on fostrox, our lead program and being able to set the recommended dose for 30 milligram within Lenvima and then to turn that around and quickly start to recruit patients into the study is very encouraging and all the feedback that we're getting from the clinicians and KOLs are very positive with regards to attractiveness of the study. There is a need to improve for this patient population and this specific combination fits very nicely with sort of the how they are approaching patients and how they are treating patients. So that's very encouraging. As exemplified by a couple of patients here today, very encouraging to see that kind of patients being able to stay on drug without progressing. And as I mentioned, the longest running patient still on treatment for now over 8 months. It's worth saying, of course, that on one hand, not everyone will respond or have benefit like this. This is a very difficult population. But it's also fair to say that we haven't shown the only 2 patients where we are seeing ability to stay on treatment. So we just want to give a little bit of a flavor on what we see, and we are looking forward sharing much more detailed data going forward. But as I mentioned, also excited about the additional data we showed at AACR with that potential opportunity for triple combinations in the future. But I think the big take-home message from this is that it builds on what we've shown before. Fostrox seems to provide very strong benefit when combined with other drugs or rather other mechanisms of action, be it PD-1s and the nonclinical models, be it with TKIs in nonclinical models or in this case, a triple combination. So it seems to find a nice position as a very strong combination partner. That's what we believe. And then as I mentioned, encouraging process across our out-licensed projects with the TNG348 molecule presenting new data and moving towards IND mid-2023. So more to come in the year. And with that, we'll stop there, and we will pause for questions.

[Operator Instructions] The next question comes from Klas Palin from Erik Penser Bank.

I just have a question about -- given your current financial position and the market environment currently, and the great opportunity seems to be with the Lenvima combo. Are you still committed to start a second track with K2 when the dose escalation part is finalized?

I think it's something we need to -- and we are watching it as we move forward. And considering that the steer we are getting towards the phase -- sort of the second line where the Lenvima combination seems to be the strategically most sound, it would seem quite natural to sort of maybe take a decision to move forward with that. But also, as I mentioned, the other arm is important for future decision purposes. So there is that element as well. So I think we're -- so there is logic just focusing at this stage for second line on the lenvatinib arm. But as the other arm does have value as well for future, I think it's a question we are pondering and working through and that we -- but of course, we need to make a decision upon that sort of recommended Phase 2 dose timing of the pembro arm.

Okay. Great. And then I have a question about the triple combination study that you presented at AACR and this address a little bit of curiosity, and I think I understand, but if use colorectal cancer model to evaluate fostrox in this type combination? And why did you do that?

Okay. Thank you for the question. So the one obvious reason, which is, of course, that living metastasis from colorectal cancer is a very common and a very problematic part of colorectal cancer treatment. But the fact is that what we've seen at diagnosis in HCC patients is that the level of DNA damage at baseline is very, very low, it's below 1%. So there's not much of DNA damage response going on in HCC patients normally. However, in syngeneic mice models, there's a lot of DNA damage going on, which means that they don't really reflect the biology of HCC patient. However, the -- this colorectal cancer cell line does. So in terms of the mechanism of action of fostrox, i.e., inducing DNA damage and creating cell death and new response, it's more relevant. So that is the reason why in this study, we chose the colorectal cancer cell.

The next question comes from Hans Engblom from EVM.

I've a few fact questions. In terms of the Phase 2a in Lenvima, how many patients are you planning to recruit?

I mean what we've said is that we will recruit in the Phase 2a up to 30 patients in total, meaning then if you split across the 2 arms, then 15 is sort of the logic sort of next number. So the first aim is to recruit sort of 15 patients in that arm. And then as per the question, sort of Klas was alluding to either. And as we look at the data, then we need to make a decision on sort of -- how do we then progress from there. But sort of the initial start is 15 patients in the Phase 2a for the lenvatinib arm, meaning that we have 4 -- sort of in this first step, we have 4 slots remaining open to reach that 15 number.

Okay. That's great. And in the fostrox pembro arm, what dose are you at the moment?

I think we've -- what we've said is that we haven't communicated dose on that arm, and we didn't do it on lenvatinib arm either. So we're kind of -- we're staying with the same approach from a communication that we will communicate the dose when we have it set and then -- so rather than sort of saying where we are and where we're moving because that might just generate sort of uncertainty, then we will communicate that when we have finalized the dose. It's sort of keeping it in line with previous kind of stringency on communication.

And I guess there is no idea to ask you when you plan to start the Phase 2b. But how long time it would from start until last -- until sort of reporting are you thinking that, that will take?

When you say from start to reporting, what do you mean, sort of for Phase 2a or?

For Phase 2b. Phase 2b...

Do you mean from initiation of Phase 2b to close of Phase 2b?

Yes.

That's pretty much an impossible question to answer because it will depend on study size and so forth. So I mean, we need to get a bit more detail from the 2a study in order to then align on the design, but more importantly, on the study size, and that will then drive sort of how quickly it will take. So I think that I could speculate wildly, but that will be...

Okay. Let me go over to what you didn't mention during the presentation. And first of all, the Xerclear with the Chinese company, SYB. Is anything happening there? Or are they looking for market approval or...?

Thank you, Hans, for the question. If -- during the pandemic, there was like a slow process in the development of that. And to be honest, they have not really carry forward from that. So it's -- we don't have any information. We're not running the program. We don't have more information at this moment. I can't give you clear answer on that.

Yes. In the interim report in respect of USP-7 and MET-X, there is a slight difference in the wording in respect of your proper -- income faring. Is that due to that there is a difference? Or is it just formulation, so to say?

The agreement for USP-7 and INFEX being revenue share agreements.

I think for USP-7, it's always been a revenue sharing agreement.

Yes, sure, sure. No, but it was just a different wording in the 2. So I just wonder whether there's sort of apart from your share, which could be different, of course. But if there's something else that is different in the agreement to?

No, they -- apart from the share, they are relatively sort of straightforward revenue share agreement. So I think I mentioned that for the last time for the INFEX part, then -- so that there are no milestone-related elements, et cetera. When INFEX -- when they out-license or sell the molecule, which they will do because they are not looking to commercialize at one point in time, then we will sort of receive a share of that sort of revenue and any sort of future revenues coming from that deal as well. So they are quite similar. So we will need to look at the wording in the report. Thank you.

Okay. The last question then in respect of INFEX. I sort of went a bit deep into it in sometimes in February and saw that Pfizer which has some of the rights for something called ATM-AVI, which was in Phase 3, which is sort of could be seen as a competitor to MET-X. Have you any information what has happened with that trial? Or is that too far away from you?

No, to be honest, I haven't followed that project. So I couldn't say what has happened. But I think not something stellar or really game-changing because then we wouldn't know.

Okay. And sort of what's your feeling in terms of the INFEX. Are they in licensing discussions? Or is it too early for that?

Now we can only speculate. But -- I mean, what they have communicated is that they're aiming to move into clinic this year. And looking at what they have done with other compounds, and I think I saw there was news around the [ Resp-X ] compound not long ago, where they had sort of clinical data. So my guess is that they will move into clinic, they will show benefit in the clinic because that's a good -- I mean that's a value evolution for them rather than licensing this early. That would be my guess, considering that the -- I mean, the likelihood that the clinic replicating preclinic in this area is quite high. So it makes sense for them to run the clinical element before moving into discussions. But then -- now I'm speculating, and I don't know.

Yes. Sure, sure. Anyhow, it seems very exciting, the molecule as such and its application.

Yes. And I think the other element to keep in mind here is that the value of MET-X will increase drastically the day the U.S. or any other governing bodies put into place a financial construct that is more encouraging, i.e., if they implement these types of [ MET-X ] models et cetera, then it will create sort of a value inflection for MET-X. I think that -- if I were them, I would keep it, develop it and wait for that to happen because I think in -- and again, now I'm speculating a bit. But in the phase of the COVID experience, I think that has triggered further commitment from authorities to find solutions for situations like this.

The next question comes from Jose Pantginis from H.C. Wainwright.

So a couple of questions. So first, I think today's call will definitely an improvement, especially with regard to the profile of fostrox, I think it's great to see not only the data in hand, but what's happening with the landscape and how the drug profile is evolving. So with that said, a couple of questions. So first, it's pretty intriguing with regard the purported impact on immune cells. And just curious with regard to the Phase 2a and looking forward, what level of translational data might you be looking at from patients in the clinic?

So the translational data that we're generating currently will be from biopsies from these patients that are in the current study. So looking at the tumor microenvironment and looking at the tumor cells. So that type of data we will be generating, and we will put into the picture for the decision-making.

Got it. And will you be doing that for future studies, including the Phase 2a or b?

For the Phase 2a, clearly, yes. for the Phase 2b, yes, but maybe a slightly smaller scope, more focused, depending on what we learn from Phase 1b and 2a.

Sure. And the focus will certainly be on the clinical efficacy. And then I think you shared a lot of important commentary today with regard to the evolution of the landscape. So with that said, it seems to have an important niche being laid out for fostrox. But is there any potential enrollment competition with other drugs? Because obviously, you delineated, you're going into later-stage patients where the options are now limited, if not zero, so just curious about any enrollment competition that might impact looking to get additional patients in the studies because obviously, you said they have interest from patients and docs.

Yes. No, I think from a competition perspective with regards to the fostrox lenvatinib arm, we're not sort of sensing any -- I would know, maybe I'm being a bit strong now looking at any competition. I mean the competition, if any, we're actually seeing between the 2 arms in the sense that it is more logical to move to Lenvima, Tecentriq, Avastin and then adding something on to Lenvima, i.e., in this case, fostrox. There seems to be a stronger tendency towards that then moving to a pembro or a PD-1 solution after Tecentriq Avastin. So there is maybe a little bit of that competition going on, which is why that arm has recruited faster. And it is also why we are including second and third-line patients. Clearly, a majority of the patients are second line. But if we're seeing third line, then we are seeing that in the pembro arm. I think that's the dynamics we are seeing. I think from other studies perspective, I know that the Imbrave, is the 250? I mean -- I think there's the Imbrave study, which is looking at sort of continuing to Tecentriq after progression on Tecentriq plus Avastin, is still recruiting, I believe. And -- but I can't say that we've heard any communication or information indicating that as a competition from a recruitment perspective known.

I think it's very, very important also to remember that fostrox is targeting the whole liver. And if you're looking -- if that is your question a little bit, it has something that we use for specific tumors in the liver, and they are combining it, I think almost everyone is combining with say, but that is not competing with the patient population that we have in our trial. So we haven't seen any new suggestions or new mechanism of action in that kind of combination right now.

Great. Interesting feedback. I appreciate it. And then lastly, I guess, sort of internal logistics type of question here. So first, where do you stand and with regard to your comfort levels around manufacturing needs for fostrox for all the clinical that's upcoming. And the second part of that question is sort of where does Medivir stand today with regard to the rightsizing of the company with regard to any personnel expansion this year or next year as everything else expands?

I'm looking at my list in how he wants to take part of the question. No, I think from a manufacturing perspective, we -- I'm not sure if we have communicated that we are working with Lonza, but we're more than happy to say that we are working with Lonza and we're quite happy with that collaboration. So on the manufacturing side, the CROs we're working with our contract development, they're working well, and we are well prepared from a sizing-up perspective. So that's not going to be a challenge whatsoever, so that we feel quite comfortable about. With regards to the sizing of the company, clearly sort of -- we feel quite comfortable where we are at the moment with the size of the company, but that will, of course, change as we move into 2b and onwards. And I think that we need to make a decision on what that could be and also potential additional opportunities with fostrox towards potentially triple, et cetera. kind of need to align on and nail down those decisions before we look at sort of potential of what will that sort of sizing up look like. At the moment, we are comfortable where we are, and we're not looking at any major changes in 2023 in the short.

There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.

Well, thank you, everyone, for calling in and engaging, asking questions. And I will just sort of take a couple of seconds to reiterate what we said, I think, a couple of times, we are very happy with the progress in Q1 on primarily our main project, fostrox, but also what we're seeing on the others. And looking forward to the rest of '23, which we believe will be quite an eventful year for the company. So with that, thank you, everyone, and have a good rest of the day.